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OBJECTIVE: To characterize surface-bound proteins and to measure the thickness of fibrin fibers bound to extracorporeal membrane oxygenation (ECMO) circuits used in children. DESIGN: Single-center observational prospective study, April to November 2021. SETTING: PICU, Royal Children's Hospital, Melbourne, Australia. PATIENTS: Patients aged less than 18 years on venoarterial ECMO and without preexisting disorder. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: ECMO circuits were collected from six patients. Circuit samples were collected from five different sites, and subsequently processed for proteomic and scanning electron microscopy (SEM) studies. The concentration of proteins bound to ECMO circuit samples was measured using a bicinchoninic acid protein assay, whereas characterization of the bound proteome was performed using data-independent acquisition mass spectrometry. The Reactome Over-representation Pathway Analyses tool was used to identify functional pathways related to bound proteins. For the SEM studies, ECMO circuit samples were prepared and imaged, and the thickness of bound fibrin fibers was measured using the Fiji ImageJ software, version 1.53c (https://imagej.net/software/fiji/). Protein binding to ECMO circuit samples and fibrin networks showed significant intra-circuit and interpatient variation. The median (range) total protein concentration was 19.0 (0-76.9) µg/mL, and the median total number of proteins was 2011 (1435-2777). A total of 933 proteins were commonly bound to ECMO circuit samples from all patients and were functionally involved in 212 pathways, with signal transduction, cell cycle, and metabolism of proteins being the top three pathway categories. The median intra-circuit fibrin fiber thickness was 0.20 (0.15-0.24) µm, whereas the median interpatient fibrin fiber thickness was 0.18 (0.15-0.21) µm. CONCLUSIONS: In this report, we have characterized proteins and fiber fibrin thickness bound to ECMO circuits in six children. The techniques and approaches may be useful for investigating interactions between blood, coagulation, and the ECMO circuit and have the potential for circuit design.

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The continuous contact between blood and the foreign surface of the extracorporeal membrane oxygenation (ECMO) circuit contributes to hemostatic, inflammatory, and other physiological disturbances observed during ECMO. Although previous studies have extensively investigated blood samples from patients on ECMO, cell adsorption to the ECMO circuit as an additional factor that could potentially influence clinical outcomes, has largely been overlooked. Here we provide a detailed immunofluorescence (IF) protocol designed to characterize cellular binding on ECMO circuits collected from patients. Extracorporeal membrane oxygenation circuits were collected from three pediatric patients and an albumin primed-only ECMO circuit was used as control. Circuit samples from five different sites within each ECMO circuit were collected and processed for the IF protocol. CD14 and CD42a antibodies were used to identify platelets and leukocytes bound to each ECMO circuit sample and images captured using inverted fluorescence microscopy. The protocol enables the comprehensive characterization of platelet and leukocyte binding to ECMO circuits collected from patients, which could in turn extend our knowledge of the characteristics of circuit binding and may provide guidance for improved ECMO circuit design.

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Air pollution health studies of fine particulate matter (diameter ≤2.5 µm, PM2.5) often use outdoor concentrations as exposure surrogates. Failure to account for variability of indoor infiltration of ambient PM2.5 and time indoors can induce exposure errors. We developed and evaluated an exposure model for individuals (EMI), which predicts five tiers of individual-level exposure metrics for ambient PM2.5 using outdoor concentrations, questionnaires, weather, and time-location information. We linked a mechanistic air exchange rate (AER) model to a mass-balance PM2.5 infiltration model to predict residential AER (Tier 1), infiltration factors (Tier 2), indoor concentrations (Tier 3), personal exposure factors (Tier 4), and personal exposures (Tier 5) for ambient PM2.5. Using cross-validation, individual predictions were compared to 591 daily measurements from 31 homes (Tiers 1-3) and participants (Tiers 4-5) in central North Carolina. Median absolute differences were 39% (0.17 h(-1)) for Tier 1, 18% (0.10) for Tier 2, 20% (2.0 µg/m(3)) for Tier 3, 18% (0.10) for Tier 4, and 20% (1.8 µg/m(3)) for Tier 5. The capability of EMI could help reduce the uncertainty of ambient PM2.5 exposure metrics used in health studies.

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Air pollution health studies often use outdoor concentrations as exposure surrogates. Failure to account for variability of residential infiltration of outdoor pollutants can induce exposure errors and lead to bias and incorrect confidence intervals in health effect estimates. The residential air exchange rate (AER), which is the rate of exchange of indoor air with outdoor air, is an important determinant for house-to-house (spatial) and temporal variations of air pollution infiltration. Our goal was to evaluate and apply mechanistic models to predict AERs for 213 homes in the Near-Road Exposures and Effects of Urban Air Pollutants Study (NEXUS), a cohort study of traffic-related air pollution exposures and respiratory effects in asthmatic children living near major roads in Detroit, Michigan. We used a previously developed model (LBL), which predicts AER from meteorology and questionnaire data on building characteristics related to air leakage, and an extended version of this model (LBLX) that includes natural ventilation from open windows. As a critical and novel aspect of our AER modeling approach, we performed a cross validation, which included both parameter estimation (i.e., model calibration) and model evaluation, based on daily AER measurements from a subset of 24 study homes on five consecutive days during two seasons. The measured AER varied between 0.09 and 3.48 h(-1) with a median of 0.64 h(-1). For the individual model-predicted and measured AER, the median absolute difference was 29% (0.19 h­1) for both the LBL and LBLX models. The LBL and LBLX models predicted 59% and 61% of the variance in the AER, respectively. Daily AER predictions for all 213 homes during the three year study (2010-2012) showed considerable house-to-house variations from building leakage differences, and temporal variations from outdoor temperature and wind speed fluctuations. Using this novel approach, NEXUS will be one of the first epidemiology studies to apply calibrated and home-specific AER models, and to include the spatial and temporal variations of AER for over 200 individual homes across multiple years into an exposure assessment in support of improving risk estimates.

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A critical aspect of air pollution exposure assessment is the estimation of the time spent by individuals in various microenvironments (ME). Accounting for the time spent in different ME with different pollutant concentrations can reduce exposure misclassifications, while failure to do so can add uncertainty and bias to risk estimates. In this study, a classification model, called MicroTrac, was developed to estimate time of day and duration spent in eight ME (indoors and outdoors at home, work, school; inside vehicles; other locations) from global positioning system (GPS) data and geocoded building boundaries. Based on a panel study, MicroTrac estimates were compared with 24-h diary data from nine participants, with corresponding GPS data and building boundaries of home, school, and work. MicroTrac correctly classified the ME for 99.5% of the daily time spent by the participants. The capability of MicroTrac could help to reduce the time-location uncertainty in air pollution exposure models and exposure metrics for individuals in health studies.

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Studies have shown that the US population continues to be exposed to polychlorinated biphenyls (PCBs), despite their ban more than three decades ago, but the reasons are not fully understood. The objectives of this paper are to characterize patterns of PCBs in blood by age, gender, and ethnicity, and identify major exposure factors. EPA's Stochastic Human Exposure and Dose Simulation (SHEDS)-dietary exposure model was applied, combining fish tissue PCB levels from a NYC Asian Market survey with National Health and Nutrition Examination Survey (NHANES) dietary consumption data, and then linked with blood biomarkers for the same NHANES study subjects. Results reveal that the mean concentration of total PCBs in blood was higher with increasing age; however, for the same age, gender, and ethnicity, the blood PCB concentrations measured in the later NHANES survey were significantly lower than those in the earlier one. The decrease within an age group between the two survey periods lessened with increasing age. Blood PCBs among different ethnicities ranked differently between the older and the younger age groups within each survey. Non-Hispanic Blacks had significantly higher blood PCBs for the >30 year age group. For the 12 to ≤30 year age group, the "Asian, Pacific Islander, Native American or multiracial" group had the highest values, with patterns fairly consistent with fish consumption and modeled PCB exposure patterns. We conclude that for younger people, patterns correspond to reduced environmental contamination over time, and are strongly associated with fish consumption and dietary exposures. Higher PCB concentrations in blood of the older population may partially reflect past exposures to higher environmental PCB concentrations, particularly before the ban.

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BACKGROUND: Both air pollution exposure and socioeconomic status (SES) are important indicators of children's health. Using highly resolved modeled predictive surfaces, we examine the joint effects of air pollution exposure and measures of SES in a population level analysis of pregnancy outcomes in North Carolina (NC). METHODS: Daily measurements of particulate matter <2.5 µm in aerodynamic diameter (PM2.5) and ozone (O3) were calculated through a spatial hierarchical Bayesian model which produces census-tract level point predictions. Using multilevel models and NC birth data from 2002-2006, we examine the association between pregnancy averaged PM2.5 and O3, individual and area-based SES indicators, and birth outcomes. RESULTS: Maternal race and education, and neighborhood household income were associated with adverse birth outcomes. Predicted concentrations of PM2.5 and O3 were also associated with an additional effect on reductions in birth weight and increased risks of being born low birth weight and small for gestational age. CONCLUSIONS: This paper builds on and complements previous work on the relationship between pregnancy outcomes and air pollution exposure by using 1) highly resolved air pollution exposure data; 2) a five-year population level sample of pregnancies; and 3) including personal and areal level measures of social determinants of pregnancy outcomes. Results show a stable and negative association between air pollution exposure and adverse birth outcomes. Additionally, the more socially disadvantaged populations are at a greater risk; controlling for both SES and environmental stressors provides a better understanding of the contributing factors to poor children's health outcomes.

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A critical aspect of air pollution exposure assessments is estimation of the air exchange rate (AER) for various buildings where people spend their time. The AER, which is the rate of exchange of indoor air with outdoor air, is an important determinant for entry of outdoor air pollutants and for removal of indoor-emitted air pollutants. This paper presents an overview and critical analysis of the scientific literature on empirical and physically based AER models for residential and commercial buildings; the models highlighted here are feasible for exposure assessments as extensive inputs are not required. Models are included for the three types of airflows that can occur across building envelopes: leakage, natural ventilation, and mechanical ventilation. Guidance is provided to select the preferable AER model based on available data, desired temporal resolution, types of airflows, and types of buildings included in the exposure assessment. For exposure assessments with some limited building leakage or AER measurements, strategies are described to reduce AER model uncertainty. This review will facilitate the selection of AER models in support of air pollution exposure assessments.

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Drosophila melanogaster is widely used to study genetic factors causing Parkinson's disease (PD) largely because of the use of sophisticated genetic approaches and the presence of a high conservation of gene sequence/function between Drosophila and mammals. However, in Drosophila, little has been done to study the environmental factors which cause over 90% of PD cases. We used Drosophila primary neuronal culture to study degenerative effects of a well-known PD toxin MPP(+) . Dopaminergic (DA) neurons were selectively degenerated by MPP(+) , whereas cholinergic and GABAergic neurons were not affected. This DA neuronal loss was because of post-mitotic degeneration, not by inhibition of DA neuronal differentiation. We also found that MPP(+) -mediated neurodegeneration was rescued by D2 agonists quinpirole and bromocriptine. This rescue was through activation of Drosophila D2 receptor DD2R, as D2 agonists failed to rescue MPP(+) -toxicity in neuronal cultures prepared from both a DD2R deficiency line and a transgenic line pan-neuronally expressing DD2R RNAi. Furthermore, DD2R autoreceptors in DA neurons played a critical role in the rescue. When DD2R RNAi was expressed only in DA neurons, MPP(+) toxicity was not rescued by D2 agonists. Our study also showed that rescue of DA neurodegeneration by Drosophila DD2R activation was mediated through suppression of action potentials in DA neurons.

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OBJECTIVES: Our primary objective was to provide higher quality, more accessible science to address challenges of characterizing local-scale exposures and risks for enhanced community-based assessments and environmental decision-making. METHODS: After identifying community needs, priority environmental issues, and current tools, we designed and populated the Community-Focused Exposure and Risk Screening Tool (C-FERST) in collaboration with stakeholders, following a set of defined principles, and considered it in the context of environmental justice. RESULTS: C-FERST is a geographic information system and resource access Web tool under development for supporting multimedia community assessments. Community-level exposure and risk research is being conducted to address specific local issues through case studies. CONCLUSIONS: C-FERST can be applied to support environmental justice efforts. It incorporates research to develop community-level data and modeled estimates for priority environmental issues, and other relevant information identified by communities. Initial case studies are under way to refine and test the tool to expand its applicability and transferability. Opportunities exist for scientists to address the many research needs in characterizing local cumulative exposures and risks and for community partners to apply and refine C-FERST.

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In recent years, there has been a trend to incorporate arterial filters into cardiopulmonary bypass (CPB) oxygenators. The FX oxygenators are the first examples of integrating a filter around the fibers of the oxygenator. To assess the efficacy of the FX05 oxygenator, in comparison with our existing CPB setup (RX05 oxygenator + arterial filter), we randomly assigned 40 patients undergoing CPB, with calculated flows <1.5 L/min, to FX05 or RX05 + arterial filter (19 FX and 21 RX). Embolic load was assessed using the emboli detection and classification quantifier, with sensors placed prefilter and postfilter/oxygenator at identical distances for both devices. A total of 6,270 FX readings and 6,183 RX readings were obtained. Because of the extremely skewed nature of the data, the prefilter embolic volumes were divided into deciles, and each decile was analyzed separately. Our results show that the devices perform similarly; both filter out a high percentage of the prefilter embolic load. Our data support that in the clinical setting, the FX05 is as effective at removing emboli as the RX05 with an arterial filter (CXAF02) which, in conjunction with the prime volume reduction and circuit simplification, has warranted our conversion to the FX series of oxygenators.

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Community-based cumulative risk assessment requires characterization of exposures to multiple chemical and non-chemical stressors, with consideration of how the non-chemical stressors may influence risks from chemical stressors. Residential radon provides an interesting case example, given its large attributable risk, effect modification due to smoking, and significant variability in radon concentrations and smoking patterns. In spite of this fact, no study to date has estimated geographic and sociodemographic patterns of both radon and smoking in a manner that would allow for inclusion of radon in community-based cumulative risk assessment. In this study, we apply multi-level regression models to explain variability in radon based on housing characteristics and geological variables, and construct a regression model predicting housing characteristics using U.S. Census data. Multi-level regression models of smoking based on predictors common to the housing model allow us to link the exposures. We estimate county-average lifetime lung cancer risks from radon ranging from 0.15 to 1.8 in 100, with high-risk clusters in areas and for subpopulations with high predicted radon and smoking rates. Our findings demonstrate the viability of screening-level assessment to characterize patterns of lung cancer risk from radon, with an approach that can be generalized to multiple chemical and non-chemical stressors.

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Despite substantial attention toward environmental tobacco smoke (ETS) exposure, previous studies have not provided adequate information to apply broadly within community-scale risk assessments. We aim to estimate residential concentrations of particulate matter (PM) from ETS in sociodemographic and geographic subpopulations in the United States for the purpose of screening-level risk assessment. We developed regression models to characterize smoking using the 2006-7 Current Population Survey--Tobacco Use Supplement, and linked these with air exchange models using the 2007 American Housing Survey. Using repeated logistic and log-linear models (n = 1000), we investigated whether household variables from the 2000 United States census can predict exposure likelihood and ETS-PM concentration in exposed households. We estimated a mean ETS-PM concentration of 16 µg/m(3) among the 17% of homes with non-zero exposure (3 µg/m(3) overall), with substantial variability among homes. The highest exposure likelihood was in the South and Midwest regions, rural populations, and low-income households. Concentrations in exposed households were highest in the South and demonstrated a non-monotonic association with income, related to air exchange rate patterns. We provide estimates of ETS-PM concentration distributions for different subpopulations in the United States, providing a starting point for communities interested in characterizing aggregate and cumulative risks from indoor pollutants.

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A critical aspect of air pollution exposure models is the estimation of the air exchange rate (AER) of individual homes, where people spend most of their time. The AER, which is the airflow into and out of a building, is a primary mechanism for entry of outdoor air pollutants and removal of indoor source emissions. The mechanistic Lawrence Berkeley Laboratory (LBL) AER model was linked to a leakage area model to predict AER from questionnaires and meteorology. The LBL model was also extended to include natural ventilation (LBLX). Using literature-reported parameter values, AER predictions from LBL and LBLX models were compared to data from 642 daily AER measurements across 31 detached homes in central North Carolina, with corresponding questionnaires and meteorological observations. Data was collected on seven consecutive days during each of four consecutive seasons. For the individual model-predicted and measured AER, the median absolute difference was 43% (0.17 h(-1)) and 40% (0.17 h(-1)) for the LBL and LBLX models, respectively. Additionally, a literature-reported empirical scale factor (SF) AER model was evaluated, which showed a median absolute difference of 50% (0.25 h(-1)). The capability of the LBL, LBLX, and SF models could help reduce the AER uncertainty in air pollution exposure models used to develop exposure metrics for health studies.

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This paper summarizes and assesses over 70 tools that could aid with gathering information and taking action on environmental issues related to community-based cumulative risk assessments (CBCRA). Information on tool use, development and research needs, was gathered from websites, documents, and CBCRA program participants and researchers, including 25 project officers who work directly with community groups. The tools were assessed on the basis of information provided by project officers, community members, CBCRA researchers, and by case study applications. Tables summarize key environmental issues and tool features: (1) a listing of CBCRA-related environmental issues of concern to communities; (2) web-based tools that map environmental information; (3) step-by-step guidance documents; (4) databases of environmental information; and (5) computer models that simulate human exposure to chemical stressors. All tools described here are publicly available, with the focus being on tools developed by the US Environmental Protection Agency. These tables provide sources of information to promote risk identification and prioritization beyond risk perception approaches, and could be used by CBCRA participants and researchers. The purpose of this overview is twofold: (1) To present a comprehensive, though not exhaustive, summary of numerous tools that could aid with performing CBCRAs; and (2) To use this toolset as a sample of the current state of CBCRA tools to critically examine their utility and guide research for the development of new and improved tools.

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Communities are faced with challenges in identifying and prioritizing environmental issues, taking actions to reduce their exposures, and determining their effectiveness for reducing human health risks. Additional challenges include determining what scientific tools are available and most relevant, and understanding how to use those tools; given these barriers, community groups tend to rely more on risk perception than science. The U.S. Environmental Protection Agency's Office of Research and Development, National Exposure Research Laboratory (NERL) and collaborators are developing and applying tools (models, data, methods) for enhancing cumulative risk assessments. The NERL's "Cumulative Communities Research Program" focuses on key science questions: (1) How to systematically identify and prioritize key chemical stressors within a given community?; (2) How to develop estimates of exposure to multiple stressors for individuals in epidemiologic studies?; and (3) What tools can be used to assess community-level distributions of exposures for the development and evaluation of the effectiveness of risk reduction strategies? This paper provides community partners and scientific researchers with an understanding of the NERL research program and other efforts to address cumulative community risks; and key research needs and opportunities. Some initial findings include the following: (1) Many useful tools exist for components of risk assessment, but need to be developed collaboratively with end users and made more comprehensive and user-friendly for practical application; (2) Tools for quantifying cumulative risks and impact of community risk reduction activities are also needed; (3) More data are needed to assess community- and individual-level exposures, and to link exposure-related information with health effects; and (4) Additional research is needed to incorporate risk-modifying factors ("non-chemical stressors") into cumulative risk assessments. The products of this research program will advance the science for cumulative risk assessments and empower communities with information so that they can make informed, cost-effective decisions to improve public health.

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